tbuckley/cabot-search huggingface dataset:
Abstract P3-02-01: Chemotherapy plus immunotherapy in stage IV triple-negative breast cancer patient during pregnancy: a case report
Authors: Candice Lima, Thiago L. Apolinario
Journal: Cancer Research (2023)

Abstract Introduction Cancer during pregnancy is uncommon but the incidence is increasing, particularly in breast cancer, the most common tumor diagnosed in this scenario. The treatment decision in pregnant patients with triple-negative breast cancer is challenging, even more so in cases with advanced disease. Clinical case A 36-year-old woman was referred to our hospital in January, 2020 with the diagnosis of an early (T2N0M0, stage IIA) invasive carcinoma of no special type triple-negative tumor on the left breast and germinative CHEK2 mutation. She received neoadjuvant treatment with four cycles of ACdd followed by nine weeks of paclitaxel and carboplatin, interrupted for local disease progression. The patient underwent a nipple-sparing mastectomy plus sentinel lymph node biopsy without complications. The pathology report showed gross residual disease, so we decided on adjuvant treatment with radiotherapy followed by capecitabine. Twelve months after the end of the treatment, she received the diagnosis of second-trimester pregnancy but also presented suspicion of pulmonary, nodal, and liver relapse. The liver biopsy confirmed triple-negative histology with CPS &amp;gt; 10. The first-line chemotherapy was liposomal doxorubicin, which showed hepatic disease progression after two cycles. As second-line, we started carboplatin, gemcitabine, and pembrolizumab. The radiologic evaluation after two cycles showed a partial response in the lung and liver, with the patient presenting excellent tolerability without fetal complications. The treatment plan is to wait until the term for delivery and continue treatment until progression or toxicity. Conclusion We report the first stage IV triple-negative breast cancer case in a pregnant patient treated with chemotherapy plus immunotherapy. This case indicates that the treatment is feasible and should be considered in this scenario. Citation Format: Candice Lima, Thiago L. Apolinario. Chemotherapy plus immunotherapy in stage IV triple-negative breast cancer patient during pregnancy: a case report [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-02-01.
Abstract P2-11-07: Association of PIK3CA mutations with efficacy in HER2-positive first-line metastatic breast cancer: a meta-analysis
Authors: Sandra Swain, Javier Cortés, Binghe Xu, Chiara Lambertini, Laurent Essioux, Adam Knott, Eleonora Restuccia, Katrin Madjar, Sanne Lysbet De Haas
Journal: Cancer Research (2023)

Abstract BACKGROUND: PIK3CA mutations have been shown to be associated with poor prognosis in HER2-positive breast cancer (BC). We combined data from three completed Phase III Roche-sponsored randomized trials of HER2-targeted therapy for the first-line treatment of HER2-positive metastatic BC (MBC); this allowed for exploration of the prognostic impact of PIK3CA mutations observed in the three individual trials across subgroups of interest. METHODS: Data from CLEOPATRA (pertuzumab + trastuzumab + docetaxel [PHD] vs. placebo [Pla] + HD; NCT00567190; N = 808), MARIANNE (HD vs. ado-trastuzumab emtansine [K] + Pla vs. K + P; NCT01120184; N = 1095), and PUFFIN (PHD vs. Pla + HD; NCT02896855; N = 243) were included. An individual patient data (IPD) meta-analysis was performed to test the association between PIK3CA mutation status in tumor tissue (mutated vs. wild type [WT]) and efficacy (progression-free and overall survival [PFS/OS]) in different biomarker and clinical subgroups. Confounder adjustment was conducted for age, Eastern Cooperative Oncology Group Performance Status, body mass index, treatment, disease type, and number of metastases (all at baseline). “Study” was included as a random effect in the IPD meta-analysis model to account for variability between studies. A landmark analysis was conducted on fast and non-fast progressors (cutoff of &amp;gt;137 days [i.e., after six chemotherapy cycles]) from CLEOPATRA and PUFFIN only, since they include the current standard-of-care regimens (PHD), by using Day 137 as the landmark time with separate Cox proportional hazards models. RESULTS: PIK3CA mutation data were available for 1905/2146 patients (89%; ~80% from primary tissue); mutation prevalence was 27% (n = 521). PIK3CA-mutated vs. WT in association with PFS in pooled treatment arms is shown in the table. OS data were consistent. CONCLUSIONS: PIK3CA mutations were associated with a worse prognosis across subgroups of interest, including in fast and non-fast progressors, in the two PHD-containing studies as compared with the overall ITT population. Table: PIK3CA-mutated vs. WT in association with PFS in pooled treatment arms Citation Format: Sandra Swain, Javier Cortés, Binghe Xu, Chiara Lambertini, Laurent Essioux, Adam Knott, Eleonora Restuccia, Katrin Madjar, Sanne Lysbet De Haas. Association of PIK3CA mutations with efficacy in HER2-positive first-line metastatic breast cancer: a meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-07.
Abstract P6-05-14: The association of sleep quality with anxiety, depression and social support in breast cancer patients with chemotherapy
Authors: Wenjuan Zhu, Wanling Li, Hui Yang, Linying Wang, Jun Guo, Jinnan Gao
Journal: Cancer Research (2023)

Abstract Background:Chemotherapy has side effects on breast cancer patients, and sleep disturbance is one of the common psychological symptoms. Purpose: This study aimed to examine the incidence of sleep disorders and investigate the relationship between anxiety and depression, hope, social support and sleep disorders in breast cancer patients with chemotherapy in China.Results:Total 350 patients were administered questionnaires, and 329 patients completed the questionnaires. The recovery rate was 94%. The majority of participants reported clinically significant sleep disturbance prior to chemotherapy (67.8%), during chemotherapy (71.8%), and after chemotherapy (72.2%). Pearson correlation analysis showed that the higher the direct support, emotional support, social interaction support, informational support and total social support score, the lower the total PSQI score of breast cancer patients (r = -0.212, -0.292, -0.236, -0.271, and -0.195 p&amp;lt; 0.01, respectively). Multifactorial model analysis showed that direct support, anxiety and age were the three main factors that affected sleep quality in breast cancer patients. Conclusions:social support may provide a powerful tool to reduce anxiety and improve sleep quality in breast cancer patients with chemotherapy. Citation Format: Wenjuan Zhu, Wanling Li, Hui Yang, Linying Wang, Jun Guo, Jinnan Gao. The association of sleep quality with anxiety, depression and social support in breast cancer patients with chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-14.
Abstract P4-09-03: Survival differences between HER2-zero and HER2-low-expressing breast cancer—A meta-analysis of early breast cancer patient data from 12 studies including 39831 patients
Authors: Xiaoqi Zhang, Ciqiu Yang, Kun Wang
Journal: Cancer Research (2023)

Abstract Background: HER2-low-expressing breast cancer takes up 40-50% in all breast cancer subtypes. Survival difference between HER2 low expression and HER2-zero breast cancer remains controversial. Therefore, the aim of this study was to compare the survival outcome of the two subtypes and to explore the impact of hormone receptor status. Methods:A comprehensive medical literature search was performed by PubMed, EMBASE, and the Cochrane Library through June 2022. We included observational studies reporting hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). The results of individual studies were pooled by fixed-effects models. Twelve articles with a total of 39,831 breast cancer patients were included in the meta-analysis. Results:We observed a statistically significant association between low HER2 expression levels and better breast cancer survival outcomes (OS: HR: 0.82; 95% confidence interval: 0.77, 0.88; DFS/RFS: HR: 0.88; 95% confidence interval: 0.83, 0.93). In a subgroup analysis, we found that HER2-low patients had better survival outcomes among hormone receptor-positive breast cancer patients (OS: HR: 0.85; 95% confidence interval: 0.78, 0.92; DFS/RFS: HR: 0.90; 95% confidence interval: 0.84, 0.96). Similarly, in triple-negative breast cancer patients, we also observed a positive association between HER2 low expression and better survival (OS: HR: 0.78; 95% confidence interval: 0.69, 0.87; DFS/RFS: HR: 0.86; 95% confidence interval: 0.77, 0.94). Conclusions: Our study showed that HER2 low expressing breast cancer had better survival outcomes compared to HER2 negative breast cancer in patients with early stage breast cancer, regardless of hormone receptor status. The result has a positive effect on us to further explore the clinical features, molecular characteristics and better treatment strategies of HER2-low-expressing breast cancer. Forest plot of HER2 low expression and overall survival in overall population Forest plot of HER2 low expression and disease free survival or relapse free survival in overall population Citation Format: Xiaoqi Zhang, Ciqiu Yang, Kun Wang. Survival differences between HER2-zero and HER2-low-expressing breast cancer—A meta-analysis of early breast cancer patient data from 12 studies including 39831 patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-09-03.
Abstract P6-05-35: Cost-effectiveness of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- metastatic breast cancer in postmenopausal women in Panama
Authors: Omar O. Castillo-Fernandez, Maria Lim, Lilian Montano
Journal: Cancer Research (2023)

Abstract Background: 4/6 kinase-dependent cyclin inhibitors have been approved for use in combination with first-line aromatase inhibitors in patients with hormone-sensitive, Her 2neu negative metastatic breast cancer. These agents have significantly improved progression-free survival compared to monotherapy aromatase inhibitors. The purpose of this study was to evaluate the cost-evaluation of each of these new agents (palbociclib, ribociclib, and abemaciclib) in the first line in Panama with the perspective of the National Oncological Institute. Methods: A partition survival analysis was carried out that includes three states (free of progression, progression, and death) with cycles of one month and a time horizon of 7.5 years. The efficacy data were taken from pivotal clinical trials, and the costs were estimated locally. A deterministic and probabilistic sensitivity analysis of the Monte Carlo was performed. Results; According to the base case, the update of each of these strategies involved an increase of USD 355,184 per additional QALY for ribociclib with Letrozole compared to Letrozole; USD 944,148/additional QALY for Palbociclib plus Letrozole; and USD 223,956 for Abemaciclib plus Letrozole, when compared with Letrozole, all above the availability threshold to pay 50,000/QALY. Conclusion: Despite the improvement in progression-free survival, none of the strategies have proved cost-effectiveness in our setting. Price negotiations, cost reduction, and risk-sharing agreements between pharmaceutical companies and payers might improve access to new drugs in countries with limited resources. Citation Format: Omar O. Castillo-Fernandez, Maria Lim, Lilian Montano. Cost-effectiveness of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- metastatic breast cancer in postmenopausal women in Panama. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-35.
Abstract P6-12-04: An Inducible Lineage Tracing System for the Identification of Tumor-Initiating Cells
Authors: Eric P. Souto, Michael T. Lewis
Journal: Cancer Research (2023)

Abstract Background: Metastasis and therapeutic resistance are a major clinical challenge, responsible for the vast majority of cancer deaths. A subpopulation of tumor cells known to have intrinsic resistance to standard therapies and contribute to metastasis function as “cancer stem”, or tumor-initiating, cells (TICs). Enriched populations of TICs are typically identified by markers such as aldehyde dehydrogenase activity, the cell surface marker combination of CD44+/CD24-, or fluorescent reporters for signaling pathways that regulate TIC function such as STAT3. Despite their utility, TIC markers and reporters have limitations. Marker expression can be unstable and there is no established method to lineage trace long-lived TICs or to follow them as they undergo cell state changes. Methods: To augment existing TIC reporters, we developed a two component TAM-inducible, Cre recombinase-dependent, STAT3 signaling-specific lentiviral LT system. The first component is a vector that labels cells with active STAT3 signaling (EGFP+), followed by a self-cleaving peptide and TAM-inducible Cre-recombinase (4M67-EGFP-P2A-CreERT2). The second component is a constitutively expressed dual-color switching Cre-dependent reporter vector (EFS-loxPdsRedloxP-mNeptune2). Addition of TAM drives color switching from dsRed to mNeptune2 via CreERT2 recombination in STAT3 signaling cells. Both lentiviral vectors were constructed using Gateway® Cloning. Sum159 cells were transduced with the LT system and reporter activity was validated both in vitro and in vivo using confocal microscopy and flow cytometry. Four LT cell populations (EGFP+/mNeptune2+, EGFP+/dsRed+, EGFP-/mNeptune2+, and EGFP-/dsRed+) were enriched using fluorescence activated cell sorting, then analyzed by single cell RNA sequencing (scRNA seq). Results: Our results confirm the STAT3 LT reporter identifies STAT3 signaling cells (EGFP+), which can be labelled (mNeptune2+) upon addition of TAM. We conducted a TAM dose response curve to identify the optimal TAM dose for complete and partial labeling of STAT3 signaling cells. scRNA seq uncovered gene expression patterns within the TIC compartment and revealed similarities and differences in gene expression between the TIC compartment and the remaining LT reporter populations. Conclusion: These data demonstrate our LT system is a powerful tool that can be applied to uncover the role of TICs in metastasis and therapeutic resistance, as well as identify genetic vulnerabilities to specifically target TICs. Citation Format: Eric P. Souto, Michael T. Lewis. An Inducible Lineage Tracing System for the Identification of Tumor-Initiating Cells [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-12-04.
Abstract P5-02-52: Predictive and prognosis value of PIK3CA mutations in HER2-positive breast cancer treated with tyrosine kinase inhibitors (TKIs): a systemic review and meta-analysis
Authors: Qiyun Shi, Juncheng Xuhong, Hao Tian, Yi Zhang, Jun Jiang, Xiaowei Qi
Journal: Cancer Research (2023)

Abstract Background: PIK3CA mutations is one of the most frequent gene alterations in breast cancers, which was reported to be related to the treatment response of anti-HER2 regimens. However, the relationship between PIK3CA mutations and treatment response of a tyrosine kinase inhibitors (TKIs) is still unclear. We thus conducted a systemic review and meta-analysis to investigate the predictive and prognosis value of PIK3CA mutations in HER2-positive breast cancer treated with TKIs. Methods: The following databases were searched from inception to July 2022: Medline, Embase and the Cochrane Library. Abstracts from conferences were also reviewed for inclusion. The critical information was extracted from eligible studies. Results: A total of 16 reports including 17 studies were assessed for eligibility, enrolling 1706 patients. Ten studies including 902 patients were in the neoadjuvant setting, the pCR rate is significantly higher in PIK3CA wild-type (WT) patients than in mutated-type (MT) patients (OR = 0.45; 95% CI: 0.31-0.65; P&amp;lt; 0.001). Seven studies including 804 patients were in the metastatic setting, the pooled objective response rate (ORR) is significantly higher in PIK3CA WT patients than in MT patients (OR = 0.40; 95% CI: 0.23-0.70; P = 0.001), and similarly, the clinical benefit rate (CBR) in WT patients is also higher (OR = 0.43; 95% CI: 0.19-0.98; P=0.045). A total of 4 metastasis studies reported progression free survival (PFS), and 2 of them reported overall survival (OS), revealing a marginally significant relationship between PIK3CA mutation and worse PFS (HR = 0.82; 95% CI: 0.67-1.00; P=0.052) and OS (HR=0.63, 95%CI:0.39-1.02; P=0.062). No evidence of publication bias was found in both the neoadjuvant setting and metastatic setting. Conclusion: Our findings indicate that PIK3CA mutations is significantly associated with a lower rate of pCR when treated with TKI-containing regimens in neoadjuvant chemotherapy of early-stage HER2-positive breast cancer, and is significantly associated with lower ORR and CBR in metastatic HER2-positive breast cancer. Citation Format: Qiyun Shi, Juncheng Xuhong, Hao Tian, Yi Zhang, Jun Jiang, Xiaowei Qi. Predictive and prognosis value of PIK3CA mutations in HER2-positive breast cancer treated with tyrosine kinase inhibitors (TKIs): a systemic review and meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-52.
Abstract P3-11-11: Impaired Succinate Metabolism Supports Endocrine Therapy Resistance in ER Positive Breast Cancers
Authors: Anil Yadav, Karla Andrade de Oliveira, Lu Jin, Robert Clarke, Surojeet Sengupta
Journal: Cancer Research (2023)

Abstract Estrogen receptor positive (ER+) breast cancer is the most common subtype among all breast cancers and is responsible for most breast cancer related deaths. Endocrine therapies, such as selective estrogen receptor modulators (SERM) and aromatase inhibitors (AI), often given in combination with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, are initially effective but the majority of advanced ER+ breast cancers eventually become refractory to endocrine therapies. Therefore, understanding the underlying molecular mechanisms that enable or promote resistance to endocrine therapies may lead to novel therapeutic targets. Cancer cells consume greater quantities of glucose to meet their energy and anabolic demands to support cell growth and proliferation. In this study, we used breast cancer cell models that are endocrine therapy sensitive and resistant and investigated the metabolites by growing the cells in the presence of the stable glucose isotope, UC13-Glucose. We measured the C13-labelled metabolites of glycolysis and the TCA cycle. Glucose consumption was higher in endocrine therapy resistant MCF7/LCC9 (LCC9) cells compared with parental MCF7 (MCF7) and estrogen independent, endocrine therapy sensitive MCF7/LCC1 (LCC1) cells. Notably, in LCC9 cells the m+4 and m+6 isotopomer of C-13 labelled citrate was absent with a concurrent high succinate:fumarate ratio. Furthermore, in LCC9 cells, most of the fumarate was unlabeled suggesting that fumarate was not generated from glucose. These results suggest that the TCA cycle is impaired in LCC9 cells and the conversion of succinate to fumarate is dysregulated. Succinate dehydrogenase (SDH) enzyme is responsible for reversible catalytic conversion of succinate to fumarate. SDH is a multimeric protein comprised of four different subunits and SDH assembly factor 2 (SDHAF2), which is a tumor suppressor gene. Comparable SDH enzyme activity was observed in LCC9 and LCC1 cells. Intriguingly, when SDH activity was inhibited using dimethylmalonate, the LCC9 cells were re-sensitized to both Fulvestrant and 4-hydroxytamoxifen. Succinate accumulation was accompanied with HIF 1-alpha stabilization and SDH inhibition led to lower levels of HIF1-alpha. This indicated that SDH may function in the conversion of fumarate to succinate in LCC9 cells. Our study further investigates the source of fumarate in LCC9 cells. Overall, this study suggests that targeting succinate metabolism may help to restore sensitivity to Fulvestrant and tamoxifen in endocrine therapy resistance in ER+ breast cancer cells. Citation Format: Anil Yadav, Karla Andrade de Oliveira, Lu Jin, Robert Clarke, Surojeet Sengupta. Impaired Succinate Metabolism Supports Endocrine Therapy Resistance in ER Positive Breast Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-11-11.